We propose to investigate several aspects of transport of Na and K, both passive and active, in erythrocytes of humans, sheep and goats. We are also interested in the functional relationships between the transport systems and other membrane elements such as enzymes and receptors. In the sheep and goats we will take advantage of the genetically determined HK-LK dimorphism of transport rates and the associated M-L blood group antigen system. We will attempt to determine the mechanism by which the L antigen in LK cells of sheep and goats keeps the Na/K pump inhibited, and how this inhibition is relieved by anti-L antibodies, resulting in stimulation of the pump. In human red cells we will investigate the mechanism of supply of ATP to the pump. We will determine if memebrane-bound glycolytic enzymes synthesize the ATP used, and if this ATP is in a membrane-bound pool. Regarding passive transport of Na and K, we will characterize Na/K cotransport in human red cells, and determine its dependence on chloride and on metabolism. In sheep red cells we will investigate the metabolic dependence passive K transport (there is no Na/K contransport). This transport system is sensitive to changes in cell volume and is inhibited by anti-L. We will attempt to characterize the "sensor" of changes in cell volume in terms of its relationship to metabolism and to the L antigen. Through these studies we hope to gain information about the mechanism of passive and active transport of Na and K, and about the modulation of transport by membrane receptors, antigens, and membrane-associated enzymes.